A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetrahydroisoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxyerythratidinone.

A titanium(III)-catalysed intermolecular reductive coupling of ketones or imines with nitriles is described, which gives direct access to α-hydroxylated and α-aminated ketones. This coupling reaction is cross-selective and a catalytic version of the classical acyloin condensation. A reaction mechanism that is supported by first DFT calculations is discussed.

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Chiral ansa-metallocenes are privileged catalysts for a range of stereoselective transformations. Their synthesis, however, has remained a tremendous challenge, which has prevented a broad and systematic exploration for applications in synthesis and catalysis. A modular approach to such ansa-metallocenes that enables a facile modification of the ring substitution and the ligand bridge, as well as the introduction of various core metals, is described. The complexes were formed with good rac-selectivity and could be isolated with high purity. The strength of the approach was demonstrated by the synthesis of several new and previously known complexes, including a unique helical chiral ansa-metallocene. Using a chiral ligand, a moderate central-to-planar chirality transfer was observed.

We herein describe the evolution of a rapid, high‐yielding synthesis of the erythrina alkaloid 3‐demethoxyerythratidinone. The natural product is assembled in six steps from commercial precursors in 30–35 % overall yield and with only two chromatographical purification operations. The key step is a titanium(III) catalyzed umpolung reaction in form of a reductive imine–nitrile coupling that can be combined with a subsequent cyclization reaction on a 50 mmol scale. Furthermore, optimized Wacker oxidation conditions enable the selective alkene oxidation in the presence of a tertiary amine functionality, which has been a problem in previous syntheses of erythrina alkaloids. The racemic route can be used to prepare the natural product on gram scale and the results may be useful for the synthesis of related alkaloids.